Variant 22-31712753-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_173566.3(PRR14L):c.5086A>G(p.Ile1696Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000374 in 1,551,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

PRR14L
NM_173566.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.142

Variant links:

Genes affected

PRR14L (HGNC:28738): (proline rich 14 like)

PRR14L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.040157586).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PRR14L	NM_173566.3 linkuse as main transcript	c.5086A>G	p.Ile1696Val	missense_variant	4/9	ENST00000327423.11	NP_775837.2	Q5THK1-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PRR14L	ENST00000327423.11 linkuse as main transcript	c.5086A>G	p.Ile1696Val	missense_variant	4/9	5	NM_173566.3	ENSP00000331845.6	Q5THK1-1
PRR14L	ENST00000431684.1 linkuse as main transcript	n.1093A>G		non_coding_transcript_exon_variant	1/5	2		ENSP00000389527.1	H7BZH1
PRR14L	ENST00000330495.8 linkuse as main transcript	c.-9A>G		upstream_gene_variant		1		ENSP00000332169.4	H3BLU3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152206

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000638

AC:

AN:

156748

Hom.:

AF XY:

0.0000845

AC XY:

AN XY:

82870

show subpopulations

Gnomad AFR exome

AF:

0.000249

Gnomad AMR exome

AF:

0.0000405

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000660

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000350

AC:

AN:

1399536

Hom.:

Cov.:

AF XY:

0.0000449

AC XY:

AN XY:

690254

show subpopulations

Gnomad4 AFR exome

AF:

0.000443

Gnomad4 AMR exome

AF:

0.0000560

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000631

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000120

Gnomad4 OTH exome

AF:

0.000241

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152324

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0000962

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000772

Hom.:

Bravo

AF:

0.000113

ExAC

AF:

0.0000389

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2024

The c.5086A>G (p.I1696V) alteration is located in exon 4 (coding exon 3) of the PRR14L gene. This alteration results from a A to G substitution at nucleotide position 5086, causing the isoleucine (I) at amino acid position 1696 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.73

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.0051

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.59

M_CAP

Benign

0.026

MetaRNN

Benign

0.040

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.49

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.21

REVEL

Benign

0.020

Sift

Benign

0.37

Sift4G

Benign

0.56

Polyphen

0.21

Vest4

0.040

MVP

0.068

MPC

0.36

ClinPred

0.020

GERP RS

0.65

Varity_R

0.012

gMVP

0.023

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over